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Clinical relevance of clonal hematopoiesis and its interference in cell-free DNA profiling of patients with gastric cancer

Authors
 Kwang Seob Lee  ;  Choong-Kun Lee  ;  Soon Sung Kwon  ;  Woo Sun Kwon  ;  Sejung Park  ;  Seung-Tae Lee  ;  Jong Rak Choi  ;  Sun Young Rha  ;  Saeam Shin 
Citation
 CLINICAL CHEMISTRY AND LABORATORY MEDICINE, Vol.62(1) : 178-186, 2024-01 
Journal Title
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
ISSN
 1434-6621 
Issue Date
2024-01
MeSH
Cell-Free Nucleic Acids* / genetics ; Clinical Relevance ; Clonal Hematopoiesis ; DNA Fingerprinting ; Hematopoiesis / genetics ; Humans ; Male ; Mutation ; Stomach Neoplasms* / genetics
Keywords
cell-free DNA ; clonal hematopoiesis ; gastric cancer ; next-generation sequencing
Abstract
Objectives: Clonal hematopoiesis (CH) is a condition in which healthy individuals have somatic mutations in hematopoietic stem cells. It has been reported with increased risk of hematologic malignancy and cardiovascular disease in the general population, but studies of Korean populations with comorbid disease entities are scarce.

Methods: White blood cells (WBCs) from patients with gastric cancer (GC) (n=121) were analyzed using a DNA-based targeted (531 genes) panel with customized pipeline designed to detect single nucleotide variants and small indels with low-allele-frequency of ≥0.2 %. We defined significant CH variants as having variant allele frequency (VAF) ≥2 % among variants found in WBCs. Matched cell-free DNA (cfDNA) samples were also analyzed with the same pipeline to investigate the false-positive results caused by WBC variants in cfDNA profiling.

Results: Significant CH variants were detected in 29.8 % of patients and were associated with age and male sex. The number of CH variants was associated with a history of anti-cancer therapy and age. DNMT3A and TET2 were recurrently mutated. Overall survival rate of treatment-naïve patients with stage IV GC was higher in those with CH, but Cox regression showed no significant association after adjustment for age, sex, anti-cancer therapy, and smoking history. In addition, we analyzed the potential interference of WBC variants in plasma cell-free DNA testing, which has attracted interest as a complementary method for tissue biopsy. Results showed that 37.0 % (47/127) of plasma specimens harbored at least one WBC variant. VAFs of interfering WBC variants in the plasma and WBC were correlated, and WBC variants with VAF ≥4 % in WBC were frequently detected in plasma with the same VAF.

Conclusions: This study revealed the clinical impact of CH in Korean patients and suggests the potential for its interference in cfDNA tests.
Full Text
https://www.degruyter.com/document/doi/10.1515/cclm-2023-0261
DOI
10.1515/cclm-2023-0261
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Sun Sung(권순성)
Kwon, Woo Sun(권우선) ORCID logo https://orcid.org/0000-0003-0268-5624
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Shin, Saeam(신새암) ORCID logo https://orcid.org/0000-0003-1501-3923
Lee, Kwang Seob(이광섭) ORCID logo https://orcid.org/0000-0002-6286-108X
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Choi, Jong Rak(최종락) ORCID logo https://orcid.org/0000-0002-0608-2989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/197279
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